BACKGROUND: Treatment options for myelofibrosis are limited. We evaluated the efficacy and safety of ruxolitinib, a potent and selective Janus kinase (JAK) 1 and 2 inhibitor, as compared with the best available therapy, in patients with myelofibrosis. METHODS: We assigned 219 patients with intermediate-2 or high-risk primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis to receive oral ruxolitinib or the best available therapy. The primary end point and key secondary end point of the study were the percentage of patients with at least a 35% reduction in spleen volume at week 48 and at week 24, respectively, as assessed with the use of magnetic resonance imaging or computed tomography. RESULTS: A total of 28% of the patients in the ruxolitinib group had at least a 35% reduction in spleen volume at week 48, as compared with 0% in the group receiving the best available therapy (P<0.001); the corresponding percentages at week 24 were 32% and 0% (P<0.001). At 48 weeks, the mean palpable spleen length had decreased by 56% with ruxolitinib but had increased by 4% with the best available therapy. The median duration of response with ruxolitinib was not reached, with 80% of patients still having a response at a median follow-up of 12 months. Patients in the ruxolitinib group had an improvement in overall quality-of-life measures and a reduction in symptoms associated with myelofibrosis. The most common hematologic abnormalities of grade 3 or higher in either group were thrombocytopenia and anemia, which were managed with a dose reduction, interruption of treatment, or transfusion. One patient in each group discontinued treatment owing to thrombocytopenia, and none discontinued owing to anemia. Nonhematologic adverse events were rare and mostly grade 1 or 2. Two cases of acute myeloid leukemia were reported with the best available therapy. CONCLUSIONS: Continuous ruxolitinib therapy, as compared with the best available therapy, was associated with marked and durable reductions in splenomegaly and disease-related symptoms, improvements in role functioning and quality of life, and modest toxic effects. An influence on overall survival has not yet been shown. (Funded by Novartis Pharmaceuticals; ClinicalTrials.gov number, NCT00934544.).
The available potential energy of the atmosphere may be defined as the difference between the total potential energy and the minimum total potential energy which could result from any adiabatic redistribution of mass. It vanishes if the density stratification is horizontal and statically stable everywhere, and is positive otherwise. It is measured approximately by a weighted vertical average of the horizontal variance of temperature. In magnitude it is generally about ten times the total kinetic energy, but less than one per cent of the total potential energy. Under adiabatic flow the sum of the available potential energy and the kinetic energy is conserved, but large increases in available potential energy are usually accompanied by increases in kinetic energy, and therefore involve nonadiabatic effects. Available potential energy may be partitioned into zonal and eddy energy by an analysis of variance of the temperature field. The zonal form may be converted into the eddy form by an eddy-transport of sensible heat toward colder latitudes, while each form may be converted into the corresponding form of kinetic energy. The general circulation is characterized by a conversion of zonal available potential energy, which is generated by low-latitude heating and high-latitude cooling, to eddy available potential energy, to eddy kinetic energy, to zonal kinetic energy.
Scattered literature is harnessed to critically review the possible sources, chemistry, potential biohazards and best available remedial strategies for a number of heavy metals (lead, chromium, arsenic, zinc, cadmium, copper, mercury and nickel) commonly found in contaminated soils. The principles, advantages and disadvantages of immobilization, soil washing and phytoremediation techniques which are frequently listed among the best demonstrated available technologies for cleaning up heavy metal contaminated sites are presented. Remediation of heavy metal contaminated soils is necessary to reduce the associated risks, make the land resource available for agricultural production, enhance food security and scale down land tenure problems arising from changes in the land use pattern.
Chest radiography is an extremely powerful imaging modality, allowing for a detailed inspection of a patient's chest, but requires specialized training for proper interpretation. With the advent of high performance general purpose computer vision algorithms, the accurate automated analysis of chest radiographs is becoming increasingly of interest to researchers. Here we describe MIMIC-CXR, a large dataset of 227,835 imaging studies for 65,379 patients presenting to the Beth Israel Deaconess Medical Center Emergency Department between 2011-2016. Each imaging study can contain one or more images, usually a frontal view and a lateral view. A total of 377,110 images are available in the dataset. Studies are made available with a semi-structured free-text radiology report that describes the radiological findings of the images, written by a practicing radiologist contemporaneously during routine clinical care. All images and reports have been de-identified to protect patient privacy. The dataset is made freely available to facilitate and encourage a wide range of research in computer vision, natural language processing, and clinical data mining.
A critical barrier to entry into structure-based virtual screening is the lack of a suitable, easy to access database of purchasable compounds. We have therefore prepared a library of 727,842 molecules, each with 3D structure, using catalogs of compounds from vendors (the size of this library continues to grow). The molecules have been assigned biologically relevant protonation states and are annotated with properties such as molecular weight, calculated LogP, and number of rotatable bonds. Each molecule in the library contains vendor and purchasing information and is ready for docking using a number of popular docking programs. Within certain limits, the molecules are prepared in multiple protonation states and multiple tautomeric forms. In one format, multiple conformations are available for the molecules. This database is available for free download (http://zinc.docking.org) in several common file formats including SMILES, mol2, 3D SDF, and DOCK flexibase format. A Web-based query tool incorporating a molecular drawing interface enables the database to be searched and browsed and subsets to be created. Users can process their own molecules by uploading them to a server. Our hope is that this database will bring virtual screening libraries to a wide community of structural biologists and medicinal chemists.
Critical care patients are monitored closely through the course of their illness. As a result of this monitoring, large amounts of data are routinely collected for these patients. Philips Healthcare has developed a telehealth system, the eICU Program, which leverages these data to support management of critically ill patients. Here we describe the eICU Collaborative Research Database, a multi-center intensive care unit (ICU)database with high granularity data for over 200,000 admissions to ICUs monitored by eICU Programs across the United States. The database is deidentified, and includes vital sign measurements, care plan documentation, severity of illness measures, diagnosis information, treatment information, and more. Data are publicly available after registration, including completion of a training course in research with human subjects and signing of a data use agreement mandating responsible handling of the data and adhering to the principle of collaborative research. The freely available nature of the data will support a number of applications including the development of machine learning algorithms, decision support tools, and clinical research.
SUMMARY: The Biopython project is a mature open source international collaboration of volunteer developers, providing Python libraries for a wide range of bioinformatics problems. Biopython includes modules for reading and writing different sequence file formats and multiple sequence alignments, dealing with 3D macro molecular structures, interacting with common tools such as BLAST, ClustalW and EMBOSS, accessing key online databases, as well as providing numerical methods for statistical learning. AVAILABILITY: Biopython is freely available, with documentation and source code at (www.biopython.org) under the Biopython license.
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The continental bio-cycling of silicon (Si) plays a key role in global Si cycle and as such partly controls global carbon (C) budget through nutrition of marine and terrestrial biota, accumulation of phytolith-occluded organic carbon (PhytOC) and weathering of silicate minerals. Despite the key role of elemental composition of phytoliths on their solubility in soils, the impact of plant cultivar and organ on the elemental composition of phytoliths in Si high-accumulator plants, such as rice (Oryza sativa) is not yet fully understood. Here we show that rice cultivar significantly impacts the elemental composition of phytoliths (Si, Al, Fe and C) in different organs of the shoot system (grains, sheath, leaf and stem). The amount of occluded OC within phytoliths is affected by contents of Si, Al and Fe in plants, while independent of the element composition of phytoliths. Our data document, for different cultivars, higher bio-available Si release from phytoliths of leaves and sheaths, which are characterized by higher enrichment with Al and Fe (i.e., lower Si/Al and Si/Fe ratios), compared to grains and stems. We indicate that phytolith solubility in soils may be controlled by rice cultivar and type of organs. Our results highlight that the role of the morphology, the hydration rate and the chemical composition in the solubility of phytoliths and the kinetic release of Si in soil solution needs to be studied further. This is central to a better understanding of the impact of soil amendment with different plant organs and cultivars on soil OC stock and on the delivery of dissolved Si as we show that sheath and leaf rice organs are both characterized by higher content of OC occluded in phytolith and higher phytolith solubility compared to grains and stems. Our study shows the importance of studying the impact of the agro-management on the evolution of sinks and sources of Si and C in soils used for Si-high accumulator plants.
Contextual word embedding models such as ELMo and BERT have dramatically improved performance for many natural language processing (NLP) tasks in recent months. However, these models have been minimally explored on specialty corpora, such as clinical text; moreover, in the clinical domain, no publicly-available pre-trained BERT models yet exist. In this work, we address this need by exploring and releasing BERT models for clinical text: one for generic clinical text and another for discharge summaries specifically. We demonstrate that using a domain-specific model yields performance improvements on 3/5 clinical NLP tasks, establishing a new state-of-the-art on the MedNLI dataset. We find that these domain-specific models are not as performant on 2 clinical de-identification tasks, and argue that this is a natural consequence of the differences between de-identified source text and synthetically non de-identified task text.
Journal Article Predicting the output from a complex computer code when fast approximations are available Get access MC Kennedy, MC Kennedy Search for other works by this author on: Oxford Academic Google Scholar A O'Hagan A O'Hagan Search for other works by this author on: Oxford Academic Google Scholar Biometrika, Volume 87, Issue 1, March 2000, Pages 1–13, https://doi.org/10.1093/biomet/87.1.1 Published: 01 March 2000
Illinois Agricultural Experiment Station 2 Chief and associate, soil fertility, department of agronomy, respectively.
The List of Bacterial Names with Standing in Nomenclature includes, alphabetically and chronologically, the official names of bacteria as published or validated in the International Journal of Systematic Bacteriology. It encompasses 5,569 taxa (as of 31 December 1996) and is available on the Internet (URL: ftp:@ftp.cict.fr/pub/ bacterio/).
Eutectic mixtures of urea and a range of quaternary ammonium salts are liquid at ambient temperatures and have interesting solvent properties.
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Ideally, questions about comparative effectiveness or safety would be answered using an appropriately designed and conducted randomized experiment. When we cannot conduct a randomized experiment, we analyze observational data. Causal inference from large observational databases (big data) can be viewed as an attempt to emulate a randomized experiment-the target experiment or target trial-that would answer the question of interest. When the goal is to guide decisions among several strategies, causal analyses of observational data need to be evaluated with respect to how well they emulate a particular target trial. We outline a framework for comparative effectiveness research using big data that makes the target trial explicit. This framework channels counterfactual theory for comparing the effects of sustained treatment strategies, organizes analytic approaches, provides a structured process for the criticism of observational studies, and helps avoid common methodologic pitfalls.
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Pathogen detection has become a major research area all over the world for water quality surveillance and microbial risk assessment. Therefore, designing simple and sensitive detection kits plays a key role in envisaging and evaluating the risk of disease outbreaks and providing quality healthcare settings. Herein, we have designed a facile and low-cost colorimetric sensing strategy for the selective and sensitive determination of β-galactosidase producing pathogens. The hexagonal boron nitride quantum dots (h-BN QDs) were established as a nanozyme that showed prominent peroxidase-like activity, which catalyzes 3,3',5,5'-tetramethylbenzidine (TMB) oxidation by H<sub>2</sub>O<sub>2</sub>. The h-BN QDs were embedded on a layer-by-layer assembled agarose biopolymer. The β-galactosidase enzyme partially degrades β-1,4 glycosidic bonds of agarose polymer, resulting in accessibility of h-BN QDs on the solid surface. This assay can be conveniently conducted and analyzed by monitoring the blue color formation due to TMB oxidation within 30 min. The nanocomposite was stable for more than 90 days and was showing TMB oxidation after incubating it with <i>Escherichia coli</i> (<i>E. coli</i>). The limit of detection was calculated to be 1.8 × 10<sup>6</sup> and 1.5 × 10<sup>6</sup> CFU/mL for <i>E. coli</i> and <i>Klebsiella pneumonia</i> (<i>K. pneumonia</i>), respectively. Furthermore, this novel sensing approach is an attractive platform that was successfully applied to detect <i>E. coli</i> in spiked water samples and other food products with good accuracy, indicating its practical applicability for the detection of pathogens in real samples.
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